公开(公告)号：US10702326B2

公开(公告)日：2020-07-07

申请号：US13550307

申请日：2012-07-16

Applicant: Robert E. Neal, II ,  Paulo A. Garcia ,  Rafael V. Davalos ,  Peter Callas

Inventor： Robert E. Neal, II ,  Paulo A. Garcia ,  Rafael V. Davalos ,  Peter Callas

IPC: A61B18/18 ,  A61B18/00 ,  A61B18/14 ,  A61B90/00

Abstract: The present invention relates to medical devices and methods for treating a lesion such as a vascular stenosis using non-thermal irreversible electroporation (NTIRE). Embodiments of the present invention provide a balloon catheter type NTIRE device for treating a target lesion comprising a plurality of electrodes positioned along the balloon that are electrically independent from each other so as to be individually selectable in order to more precisely treat an asymmetrical lesion in which the lesion extends only partially around the vessel.

公开(公告)号：US20190282294A1

公开(公告)日：2019-09-19

申请号：US16352759

申请日：2019-03-13

Applicant: RAFAEL V. DAVALOS ,  NATALIE BEITEL WHITE ,  NIKOLAOS DERVISIS ,  IRVING COY ALLEN

Inventor： RAFAEL V. DAVALOS ,  NATALIE BEITEL WHITE ,  NIKOLAOS DERVISIS ,  IRVING COY ALLEN

IPC: A61B18/14 ,  A61K31/282 ,  A61K31/4745 ,  A61K31/513 ,  A61K31/519

Abstract: Described herein are methods of performing immunotherapy on a subject and/or determining if a subject will be responsive to ablation immunotherapy.

公开(公告)号：US08992517B2

公开(公告)日：2015-03-31

申请号：US12491151

申请日：2009-06-24

Applicant: Rafael V. Davalos ,  Paulo A. Garcia ,  John H. Rossmeisl ,  John L. Robertson ,  Robert E. Neal

Inventor： Rafael V. Davalos ,  Paulo A. Garcia ,  John H. Rossmeisl ,  John L. Robertson ,  Robert E. Neal

IPC: A61B18/14 ,  A61N1/32 ,  C12N13/00 ,  A61N1/05

CPC classification number: A61B18/1477 ,  A61B18/1206 ,  A61B2018/00446 ,  A61B2018/00613 ,  A61N1/05 ,  A61N1/327 ,  C12N13/00

Abstract: The present invention provides methods, devices, and systems for in vivo treatment of cell proliferative disorders. The invention can be used to treat solid tumors, such as brain tumors. The methods rely on non-thermal irreversible electroporation (IRE) to cause cell death in treated tumors.

Abstract translation: 本发明提供用于体内治疗细胞增殖性疾病的方法，装置和系统。 本发明可用于治疗诸如脑肿瘤的实体瘤。 该方法依赖于非热不可逆电穿孔（IRE）在治疗的肿瘤中引起细胞死亡。

公开(公告)号：US20130253415A1

公开(公告)日：2013-09-26

申请号：US13989175

申请日：2011-11-23

Applicant: Michael B. Sano ,  Rafael V. Davalos ,  John L. Robertson ,  Paulo A. Garcia ,  Robert E. Neal

Inventor： Michael B. Sano ,  Rafael V. Davalos ,  John L. Robertson ,  Paulo A. Garcia ,  Robert E. Neal

IPC: A61B18/14 ,  A61M5/00

CPC classification number: A61B18/14 ,  A61B18/1492 ,  A61B2018/00613 ,  A61B2018/1472 ,  A61B2218/002 ,  A61K48/0075 ,  A61M5/00 ,  A61N1/327

Abstract: The present invention relates to the field of medical treatment of diseases and disorders, as well as the field of biomedical engineering. Embodiments of the invention relate to the delivery of Irreversible Electroporation (IRE) through the vasculature of organs to treat tumors embedded deep within the tissue or organ, or to decellularize organs to produce a scaffold from existing animal tissue with the existing vasculature intact. In particular, methods of administering non-thermal irreversible electroporation (IRE) in vivo are provided for the treatment of tumors located in vascularized tissues and organs. Embodiments of the invention further provide scaffolds and tissues from natural sources created using IRE ex vivo to remove cellular debris, maximize recellularization potential, and minimize foreign body immune response. The engineered tissues can be used in methods of treating subjects, such as those in need of tissue replacement or augmentation.

Abstract translation: 本发明涉及疾病和病症的医疗领域以及生物医学工程领域。 本发明的实施方案涉及通过器官脉管系统递送不可逆电穿孔（IRE）以治疗深入组织或器官内的肿瘤，或者使现有动物组织脱细胞从而使现有的脉管系统完整地产生支架。 特别地，提供了在体内施用非热不可逆电穿孔（IRE）的方法用于治疗位于血管化组织和器官中的肿瘤。 本发明的实施方案进一步提供了使用IRE离体产生的来自天然来源的支架和组织，以去除细胞碎片，最大限度地获得细胞结合潜能，并使异物免疫应答最小化。 工程组织可用于治疗受试者的方法，例如需要组织置换或增生的方法。

公开(公告)号：US20120190078A1

公开(公告)日：2012-07-26

申请号：US13498657

申请日：2010-09-28

Applicant: Paul Gatenholm ,  Henrik Backdahl ,  Theodore Jon Tzavaras ,  Rafael V. Davalos ,  Michael B. Sano

Inventor： Paul Gatenholm ,  Henrik Backdahl ,  Theodore Jon Tzavaras ,  Rafael V. Davalos ,  Michael B. Sano

IPC: C12P19/04 ,  C12N5/02 ,  C12N11/12

CPC classification number: C08B1/00 ,  A61L27/20 ,  A61L27/38 ,  A61L27/56 ,  A61L2400/12 ,  C12N5/0062 ,  C12N11/12 ,  C12N2533/78 ,  C12P19/04 ,  C08L1/02

Abstract: A novel BC fermentation technique for controlling 3D shape, thickness and architecture of the entangled cellulose nano-fibril network is presented. The resultant nano-cellulose based structures are useful as biomedical implants and devices, are useful for tissue engineering and regenerative medicine, and for health care products. More particularly, embodiments of the present invention relate to systems and methods for the production and control of 3-D architecture and morphology of nano-cellulose biomaterials produced by bacteria using any biofabrication process, including the novel 3-D Bioprinting processes disclosed. Representative processes according to the invention involve control of the rate of production of biomaterial by bacteria achieved by meticulous control of the addition of fermentation media using a microfluidic system. In exemplary embodiments, the bacteria gradually grew up along the printed alginate structure that had been placed into the culture, incorporating it. After culture, the printed alginate structure was successfully removed revealing porosity where the alginate had been placed. Porosity and interconnectivity of pores in the resultant 3-D architecture can be achieved by porogen introduction using, e.g., ink-jet printer technology.

Abstract translation: 提出了一种用于控制缠结纤维素纳米纤维网络的3D形状，厚度和结构的新型BC发酵技术。 所得的纳米纤维素基结构可用作生物医学植入物和装置，可用于组织工程和再生医学以及保健产品。 更具体地说，本发明的实施方案涉及使用任何生物制造方法生产和控制由细菌生产的纳米纤维素生物材料的三维结构和形态的系统和方法，包括所公开的新型3-D生物印迹方法。 根据本发明的代表性方法涉及通过细微控制使用微流体系统添加发酵培养基来控制细菌生物材料的生产速率。 在示例性实施方案中，细菌沿已经放入培养物中的印刷的藻酸盐结构逐渐长大，并入其中。 培养后，成功去除了印刷的藻酸盐结构，显示了藻酸盐放置的孔隙度。 所得3-D结构中孔隙的孔隙率和互连性可以通过使用例如喷墨打印机技术的致孔剂引入来实现。

公开(公告)号：US20110106221A1

公开(公告)日：2011-05-05

申请号：US12906923

申请日：2010-10-18

Applicant: Robert E. Neal, II ,  Paulo A. Garcia ,  Rafael V. Davalos ,  John H. Rossmeisl ,  John L. Robertson

Inventor： Robert E. Neal, II ,  Paulo A. Garcia ,  Rafael V. Davalos ,  John H. Rossmeisl ,  John L. Robertson

IPC: A61N1/32 ,  A61N1/00 ,  G06F17/50

CPC classification number: C12N13/00 ,  A61B34/10 ,  A61B2018/00613 ,  A61B2034/104 ,  A61B2034/105 ,  A61N1/0412 ,  G16H50/50

Abstract: The present invention provides systems, methods, and devices for electroporation-based therapies (EBTs). Embodiments provide patient-specific treatment protocols derived by the numerical modeling of 3D reconstructions of target tissue from images taken of the tissue, and optionally accounting for one or more of physical constraints or dynamic tissue properties. The present invention further relates to systems, methods, and devices for delivering bipolar electric pulses for irreversible electroporation exhibiting reduced or no damage to tissue typically associated with an EBT-induced excessive charge delivered to the tissue.

Abstract translation: 本发明提供了用于基于电穿孔的疗法（EBT）的系统，方法和装置。 实施例提供了通过从组织拍摄的图像对目标组织进行3D重建的数值模拟得出的患者特异性治疗方案，并且可选地考虑物理约束或动态组织属性中的一种或多种。 本发明还涉及用于递送用于不可逆电穿孔的双极电脉冲的系统，方法和装置，其显示对EBT诱导的递送至组织的过量电荷通常相关的组织的减少或不损伤。

公开(公告)号：US10078066B2

公开(公告)日：2018-09-18

申请号：US14636646

申请日：2015-03-03

Applicant: Rafael V. Davalos ,  Hadi Shafiee ,  Michael Benjamin Sano ,  John L. Caldwell

Inventor： Rafael V. Davalos ,  Hadi Shafiee ,  Michael Benjamin Sano ,  John L. Caldwell

IPC: G01N27/447 ,  B03C5/00 ,  B03C5/02 ,  B01D57/02

CPC classification number: G01N27/44791 ,  B01D57/02 ,  B03C5/005 ,  B03C5/022 ,  B03C5/026 ,  B03C2201/26

Abstract: Devices and methods for performing dielectrophoresis are described. The devices contain sample channel which is separated by physical barriers from electrode channels which receive electrodes. The devices and methods may be used for the separation and analysis of particles in solution, including the separation and isolation of cells of a specific type. As the electrodes do not make contact with the sample, electrode fouling is avoided and sample integrity is better maintained.

公开(公告)号：US09598691B2

公开(公告)日：2017-03-21

申请号：US12432295

申请日：2009-04-29

Applicant: Rafael V. Davalos

Inventor： Rafael V. Davalos

IPC: C12N13/00 ,  A61K35/12 ,  C12N5/00

CPC classification number: A61L27/3691 ,  A61K35/12 ,  A61L27/3604 ,  A61L27/3625 ,  A61L27/3633 ,  A61L27/38 ,  A61L2430/28 ,  A61L2430/40 ,  C12N5/0068 ,  C12N13/00 ,  C12N2533/90

Abstract: The present invention provides engineered tissue scaffolds, engineered tissues, and methods of using them. The scaffolds and tissues are derived from natural tissues and are created using non-thermal irreversible electroporation (IRE). Use of IRE allows for ablation of cells of the tissue to be treated, but allows vascular and neural structures to remain essentially unharmed. Use of IRE thus permits preparation of thick tissue scaffolds and tissues due to the presence of vasculature within the scaffolds. The engineered tissues can be used in methods of treating subjects, such as those in need of tissue replacement or augmentation.

公开(公告)号：US08968542B2

公开(公告)日：2015-03-03

申请号：US12720406

申请日：2010-03-09

Applicant: Rafael V. Davalos ,  Hadi Shafiee ,  Michael B. Sano ,  John L. Caldwell

Inventor： Rafael V. Davalos ,  Hadi Shafiee ,  Michael B. Sano ,  John L. Caldwell

IPC: B01D57/02 ,  B03C5/02 ,  B03C5/00

CPC classification number: G01N27/44791 ,  B01D57/02 ,  B03C5/005 ,  B03C5/022 ,  B03C5/026 ,  B03C2201/26

Abstract: Devices and methods for performing dielectrophoresis are described. The devices contain sample channel which is separated by physical barriers from electrode channels which receive electrodes. The devices and methods may be used for the separation and analysis of particles in solution, including the separation and isolation of cells of a specific type. As the electrodes do not make contact with the sample, electrode fouling is avoided and sample integrity is better maintained.

Abstract translation: 描述了用于进行介电电泳的装置和方法。 这些器件包含由接收电极的电极通道的物理屏障分离的样品通道。 该装置和方法可用于分离和分析溶液中的颗粒，包括分离和分离特定类型的细胞。 由于电极不与样品接触，避免了电极结垢，更好地保持了样品的完整性。

公开(公告)号：US20140339088A1

公开(公告)日：2014-11-20

申请号：US14449050

申请日：2014-07-31

Applicant: Eva M. Schmelz ,  Elizabeth S. Elvington ,  Alireza Salmanzadeh ,  Mike Sano ,  Paul C. Roberts ,  Rafael V. Davalos

Inventor： Eva M. Schmelz ,  Elizabeth S. Elvington ,  Alireza Salmanzadeh ,  Mike Sano ,  Paul C. Roberts ,  Rafael V. Davalos

IPC: G01N33/487 ,  G01N27/447 ,  G01N33/50

CPC classification number: G01N33/48735 ,  B03C5/005 ,  B03C5/026 ,  B03C2201/26 ,  G01N27/44704 ,  G01N33/5011 ,  G01N33/5023

Abstract: Provided are dielectrophoresis (DEP) devices and methods that allow cell sorting to identify, isolate, and/or separate cells of interest based on electrical and physical properties of the cells. Particularly, provided are systems and methods for manipulating particles suspended in a fluid, e.g., cells, micro- or nano-particles, using their electrical signatures. Such methods can be performed using DEP, iDEP, and/or cDEP (contactless dielectrophoresis, where direct contact between the electrodes and the sample is avoided). Typically, an electric field is induced in a sample comprising the target particles and/or cells, such as cancer cells, and the spatial distribution of cells is measured to identify one or more characteristics or properties of the cancer cells. The identified characteristics of the sorted cells can be used to determine drug efficacy and/or resistance with respect to the cells.

Abstract translation: 提供的是介电电泳（DEP）装置和方法，其允许细胞分选基于细胞的电学和物理性质鉴定，分离和/或分离感兴趣的细胞。 特别地，提供了使用其电特征来操纵悬浮在流体中的颗粒（例如，细胞，微米或纳米颗粒）的系统和方法。 可以使用DEP，iDEP和/或cDEP（非接触式介电电泳，其中避免了电极和样品之间的直接接触）来执行这些方法。 通常，在包含靶颗粒和/或细胞（例如癌细胞）的样品中诱导电场，并且测量细胞的空间分布以鉴定癌细胞的一个或多个特征或性质。 分选的细胞的鉴定特征可用于确定相对于细胞的药物功效和/或抗性。